From the Guidelines
A positive ANA test requires a comprehensive diagnostic workup to determine its clinical significance, including a detailed medical history, physical examination, and additional autoantibody tests, as recommended by the most recent guidelines 1. The diagnostic workup for a positive ANA test should prioritize the following steps:
- Detailed medical history and physical examination to identify any symptoms or signs suggestive of an autoimmune disease
- Additional autoantibody tests, including:
- Anti-dsDNA
- Anti-Sm
- Anti-RNP
- Anti-SSA/Ro and Anti-SSB/La
- Anti-Scl-70
- Anti-centromere
- Complete blood count (CBC) with differential
- Comprehensive metabolic panel
- Urinalysis
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
- Complement levels (C3 and C4) It is essential to interpret the results of these tests in the context of the patient's clinical presentation, as a positive ANA test can be found in healthy individuals or in various non-autoimmune conditions 1. The pattern and titer of ANA, along with specific autoantibodies, can provide clues to the underlying condition. The use of a double-screening strategy for anti-dsDNA testing, using a last-generation solid-phase assay (SPA) followed by the Crithidia luciliae immunofluorescence test (CLIFT) as a confirmation test, is recommended 1. This approach helps minimize false positive results and ensures accurate diagnosis. In cases where the SPA is positive, and the CLIFT is negative, the diagnosis of SLE should not be ruled out, and further testing, such as anti-nucleosome or antiphospholipid antibodies, may be necessary to support the diagnosis 1. Overall, a comprehensive diagnostic workup, including a detailed medical history, physical examination, and additional autoantibody tests, is essential to determine the clinical significance of a positive ANA test and to guide further management and treatment.
From the Research
Diagnostic Workup for Positive Antinuclear Antibody (ANA) Test
The diagnostic workup for a positive ANA test involves several steps to determine the underlying cause of the positive result.
- A positive ANA test can be seen in various conditions, including systemic autoimmune diseases such as systemic lupus erythematosus (SLE) 2, as well as in non-autoimmune inflammatory diseases, including acute and chronic infections 2, 3.
- The initial manifestations of patients with high and low titers of ANA can vary, with joint pain being the most common initial presentation 4.
- Patients with high ANA titers (≥ 1:640) are more susceptible to autoimmune diseases, especially those presenting with joint pain, fever, abnormal urinalysis, or skin rash/skin tightness 4.
- A risk model has been developed to predict the risk of developing autoimmune disease in individuals with a positive ANA test, taking into account demographics, billing codes for autoimmune disease-related symptoms, and laboratory values 5.
- The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals 5.
- Different methods for ANA screening, such as indirect immunofluorescence (IIF), addressable laser bead immunoassay (ALBIA), and fluorescence enzyme immunoassay (FEIA), have varying diagnostic performances, with IIF showing the highest frequency of positive ANA and ALBIA showing high sensitivity for autoimmune disease 6.
- The choice of ANA screening method may depend on the pre-test probability of systemic autoimmune disease, with IIF being more suitable for high pre-test probability populations and solid-phase assays being more useful in populations with a low pre-test probability 6.